Bioanalytical method development for polmacoxib in rat plasma using LC-MS/MS and Its preclinical pharmacokinetic...

To develop and validate a rapid, sensitive, and selective LC - MS/MS method for quantifying polmacoxib (POL) in rat plasma and integrating for preclinical pharmacokinetic evaluation.

POL was quantified using LC - MS/MS on a Varian C8 column with an isocratic mobile phase of methanol and 2 mM ammonium acetate (90:10, v/v; 0.4 mL/min) with run time of 6 min. Detection employed negative ion electrospray and MRM (m/z 360 → 296 for POL; m/z 313 → 257 for rofecoxib as IS). The method was validated as per USFDA guidelines. Male Sprague - Dawley rats received a single oral dose of 10 mg/kg POL, and plasma samples were collected up to 72 h.

The method showed linearity (1.56-800 ng/mL, r²  = 0.9994), LLOQ 1.56 ng/mL, and acceptable accuracy, precision, recovery, and matrix effects. Pharmacokinetics: Cmax 643 ± 32 ng/mL, Tmax 4 h, T1/2 10.4 ± 0.8 h, AUC₀-∞ 5326 ± 106 ng*h/mL.

The validated assay is robust, sensitive, and suitable for pharmacokinetic, bioequivalence, and drug - drug interaction studies of POL.